Invariant chain+ N2a neuroblastoma cells stably expressing the class II MHC transactivator CIITA fail to stimulate anti-tumor immunity.
A promising cancer treatment strategy involves stimulation of anti-tumor immune responses. CD4(+) T cell responses are particularly desirable, as they enhance CD8(+) T cell activity and provide immune memory. The major histocompatibility complex (MHC) class II transactivator CIITA can be used to stimulate expression of MHC II on tumor cells, thereby promoting CD4(+) T cell activation. In this study, N2a neuroblastoma cells were stably transfected with CIITA. N2aCIITA cells displayed increased expression of MHC I, MHC II and invariant chain; CD80 and CD86 were expressed by neither the parental N2a cells nor by the N2aCIITA cells. All mice injected with N2aCIITA cells developed tumors. Furthermore, no increase in the numbers of T cells, natural killer cells, macrophages, or eosinophils was observed in the spleens or tumors of mice injected with N2aCIITA cells, compared to tissues from mice injected with the parental N2a cells. This absence of an anti-tumor immune response despite MHC II expression is likely due to the presence of invariant chain, in support of the MHCII(+)/Ii(-) paradigm.
Rickard
Steve
S
Dobbs Ocular Immunology Laboratories, Emory Eye Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Ono
Santa Jeremy
SJ
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D007109:Immunity / Q000276:immunology*; D007700:Kinetics; D051379:Mice; D009447:Neuroblastoma / Q000276:immunology* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism*; D010641:Phenotype; D013154:Spleen / Q000276:immunology / Q000473:pathology; D015534:Trans-Activators / Q000378:metabolism*
D000944:Antigens, Differentiation, B-Lymphocyte; D015415:Biomarkers; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators; C045084:invariant chain